Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background & Aims: Aflatoxin exposure increases the risk for hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected individuals, particularly males. We investigated sex-based differences in the HCC genome and antitumor immunity.
Methods: Whole-genome, whole-exome, and RNA sequencing were performed on 101 HCC patient samples (47 males, 54 females) that resulted from HBV infection and aflatoxin exposure from Qidong. Androgen on the expression of aflatoxin metabolism-related genes and nonhomologous DNA end joining (NHEJ) factors were examined in HBV-positive HCC cell lines, and further tested in tumor-bearing syngeneic mice.
Results: Qidong HCC differed between males and females in genomic landscape and transcriptional dysfunction pathways. Compared with females, males expressed higher levels of aflatoxin metabolism-related genes, such as AHR and CYP1A1, and lower levels of NHEJ factors, such as XRCC4, LIG4, and MRE11, showed a signature of up-regulated type I interferon signaling/response and repressed antitumor immunity. Treatment with AFB in HBV-positive cells, the addition of 2 nmol/L testosterone to cultures significantly increased the expression of aflatoxin metabolism-related genes, but reduced NHEJ factors, resulting in more nuclear DNA leakage into cytosol to activate cGAS-STING. In syngeneic tumor-bearing mice that were administrated tamoxifen daily via oral gavage, favorable androgen signaling repressed NHEJ factor expression and activated cGAS-STING in tumors, increasing T-cell infiltration and improving anti-programmed cell death protein 1 treatment effect.
Conclusions: Androgen signaling in the context of genotoxic stress repressed DNA damage repair. The alteration caused more nuclear DNA leakage into cytosol to activate the cGAS-STING pathway, which increased T-cell infiltration into tumor mass and improved anti-programmed cell death protein 1 immunotherapy in HCCs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772570 | PMC |
| http://dx.doi.org/10.1016/j.jcmgh.2022.10.009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Lysine Succinylation of VBS Contributes to Sclerotia Development and Aflatoxin Biosynthesis in Aspergillus flavus.
Mol Cell Proteomics
February 2023
State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chine
Aspergillus flavus is a common saprophytic and pathogenic fungus, and its secondary metabolic pathways are one of the most highly characterized owing to its aflatoxin (AF) metabolite affecting global economic crops and human health. Different natural environments can cause significant variations in AF synthesis. Succinylation was recently identified as one of the most critical regulatory post-translational modifications affecting metabolic pathways.
View Article and Find Full Text PDFSex Differences in Genomic Features of Hepatitis B-Associated Hepatocellular Carcinoma With Distinct Antitumor Immunity.
Cell Mol Gastroenterol Hepatol
January 2023
State Key Lab of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; Immunology Department, National Cancer Center, National Clinical Research Center for Cancer,
Background & Aims: Aflatoxin exposure increases the risk for hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected individuals, particularly males. We investigated sex-based differences in the HCC genome and antitumor immunity.
Methods: Whole-genome, whole-exome, and RNA sequencing were performed on 101 HCC patient samples (47 males, 54 females) that resulted from HBV infection and aflatoxin exposure from Qidong.
SfgA Renders More Stable to the External Environment.
J Fungi (Basel)
June 2022
The Guangdong Province Key Laboratory for Aquatic Economic Animals, School of Life Science, Sun Yat-sen University, Guangzhou 510275, China.
is known as a key negative transcriptional regulator gene of asexual sporulation and sterigmatocystin production in . However, here, we found that the homolog gene shows a broad and complex regulatory role in governing growth, conidiation, sclerotia formation, secondary metabolism, and environmental stress responses in . When was deleted in the fungal growth was slowed, but the conidiation was significantly increased, and the sclerotia formation displayed different behavior at different temperatures, which increased at 30 °C but decreased at 36 °C.
View Article and Find Full Text PDFComprehensive Transcriptome and Proteome Analyses Reveal the Modulation of Aflatoxin Production by on Different Crop Substrates.
Front Microbiol
July 2020
Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs/Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, China.
As a natural severe contaminant of stored grains and other crops worldwide, can produce aflatoxins (AFs), the most powerful naturally producing toxic and hepatocarcinogenic compounds. AFs production is regulated by diverse factors including AFs cluster genes, transcription factors, regulators, and environmental factors. Among them, crop substrate is one of the most important factors.
View Article and Find Full Text PDFLiver-Kidney-on-Chip To Study Toxicity of Drug Metabolites.
ACS Biomater Sci Eng
January 2018
Institute of Pharmacy and Molecular Biotechnology, Pharmaceutical Biology, Heidelberg University, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
Advances in organ-on-chip technologies for the application in in vitro drug development provide an attractive alternative approach to replace ethically controversial animal testing and to establish a basis for accelerated drug development. In recent years, various chip-based tissue culture systems have been developed, which are mostly optimized for cultivation of one single cell type or organoid structure and lack the representation of multi organ interactions. Here we present an optimized microfluidic chip design consisting of interconnected compartments, which provides the possibility to mimic the exchange between different organ specific cell types and enables to study interdependent cellular responses between organs and demonstrate that such tandem system can greatly improve the reproducibility and efficiency of toxicity studies.
View Article and Find Full Text PDF